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Drug Update| December 15 2020 Erin D. Wieruszewski, PharmD, BCCCP; Erin D. Wieruszewski, PharmD, BCCCP Erin D. Wieruszewski is Clinical Pharmacy Specialist, Emergency Medicine and Neurocritical Care, Mayo Clinic, Department of Pharmacy, 1216 2nd Street SW, Rochester, MN 55902 (). Search for other works by this author on: Caitlin S. Brown, PharmD, BCCCP; Caitlin S. Brown, PharmD, BCCCP Caitlin S. Brown is Clinical Pharmacy Specialist, Emergency Medicine and Neurocritical Care, Mayo Clinic, Department of Pharmacy, Rochester, Minnesota. Search for other works by this author on: Jonathan G. Leung, PharmD, BCPS, BCPP; Jonathan G. Leung, PharmD, BCPS, BCPP Jonathan G. Leung is Clinical Pharmacy Specialist, Psychiatry, Mayo Clinic, Department of Pharmacy, Rochester, Minnesota. Search for other works by this author on: Patrick M. Wieruszewski, PharmD, BCCCP Patrick M. Wieruszewski, PharmD, BCCCP Patrick M. Wieruszewski is Clinical Pharmacy Specialist, Cardiothoracic Surgery and Anesthesia Critical Care, Mayo Clinic, Department of Pharmacy, Rochester, Minnesota. Search for other works by this author on: AACN Adv Crit Care (2020) 31 (4): 349–356.
Status epilepticus (SE) is a neurological emergency defined as 5 minutes or more of continuous seizure activity or recurrent seizures without a return to baseline between seizures.1 Previous definitions required seizure activity to last for at least 30 minutes before being considered SE. However, earlier intervention is required to reduce morbidity and mortality from permanent neuronal damage.2 Treatment of SE centers on rapid control of seizures with benzodiazepines in the emergent-control phase, followed by urgent-control therapy with intravenous antiepileptic drugs (AEDs) to prevent further seizures.3 Patients whose seizures do not respond to adequate urgent- and emergent-control therapy are considered to have refractory SE (RSE). The longer patients’ seizures last, the more difficult it is to terminate the seizures, often requiring multiple AEDs, intubation, and continuous-infusion anesthetic medications to achieve seizure termination.1 Status epilepticus should be treated with rapidly administered, appropriately dosed benzodiazepines followed by intravenous AEDs.... You do not currently have access to this content. Sign inSubscribeSubscribe online and gain access to the entire archive. Short-term AccessPurchase short-term access on a pay-per-article or pay-per-issue basis. $15 72 - hour single article access $30 7 - day full issue access 269 Views 2 Web of Science 2 Crossref Cited ByEmail alertsJeffrey L. Segar, MD, Danielle R. Rios MD, MS, John M. Dagle, MD, PhD, and Sarah B. Tierney PharmD Jeffrey L. Segar, MD, Danielle R. Rios MD, MS, Elizabeth W. Amelon, Pharm.D., BCPS, Sarah B. Tierney,
Pharm.D. Systemic narcotics are the most commonly used agents for management of pain in the post-operative patient. They are also the most frequently used agents given to ventilated children, particularly when paralyzed with neuromuscular blockers, or those with bronchopulmonary dysplasia. Download Analgesics and Sedatives Table Jeffrey L. Segar, MD and Sarah B. Tierney, PharmD Agents should always be used in concert with adequate
sedatives and analgesics
(0.1 mg/kg/h for continuous infusion) Dosing interval: 60-120 minutes Protein binding: 60-80% Dosing interval: 60-120 minutes Protein binding: 87% Do not give IM Dosing interval: 10-30 minutes Protein binding: 30% *Depolarizing agents are not routinely recommended because they persist for a longer duration due to their resistance to acetylcholinesterase. References:
AnticonvulsantsJeffrey L. Segar, MD and Sarah B. Tierney, PharmD
Footnotes:
References:
AntimicrobialsSarah Tierney,
Pharm.D. and Jonathan Klein, MD Gentamicin peak and trough guidelines1
Gentamicin is a concentration-dependent, bactericidal antibiotic used for the treatment of gram-negative organisms including Pseudomonas, Escherichia coli, Proteus, and Serratia. It is also used in combination with ampicillin for treatment of gram-positive group B Streptococcus species and Listeria monocytogenes. The rationale for using the extended-interval dosing protocol for gentamicin is based on the concentration-dependent bactericidal activity of aminoglycosides, the extended post-antibiotic effect, and the possibility of reduced nephrotoxicity and ototoxicity.1,2 Bactericidal effectsThe current gentamicin dosing protocol (Neofax) achieves an early and high peak gentamicin plasma concentration for optimal bactericidal effect about 94% of the time.3,4 In vitro, aminoglycosides eradicate bacteria at a rate proportional to the peak concentration attained. Therefore, a high peak level results in a more rapid and efficient bactericidal effect against susceptible organisms. In addition, aminoglycosides have an extended post-antibiotic effect (PAE) which is defined as the time period that surviving bacteria, following exposure to an antibiotic, cannot metabolize or multiply even though extracellular antibiotic is no longer present. The duration of PAE is approximately 8-12 hours in the immunocompromised patient.1 Potential toxicityThe uptake of aminoglycosides occurs in the renal tubular cells and is a saturable process; therefore, larger doses would not be expected to be any more nephrotoxic than smaller doses. Both animal and human studies have shown that the concentration in the renal cortex is significantly lower when administered as a single daily dose than when divided and administered more frequently. Animal data supports an accumulation threshold in the organ of Corti as well, so there is the potential for less ototoxicity.1,5 Although neonates are believed to experience a lower risk for ototoxicity and nephrotoxicity than adults;5 sustained elevated peak (>12 mg/L) or trough (>2 mg/L) concentrations may cause these toxicities in neonates.3 References
Edward F. Bell, MD and Jeffrey L. Segar, MD This nomogram is for use only in term neonates (<30 days old) receiving gentamicin or tobramycin 2.5 mg/kg given IV every 12 hours. Illustration of the upper and lower range of acceptable gentamicin serum concentrations (heavy dashed and solid parallel lines). The mean + S.D. for the peak serum gentamicin concentrations of 81 neonates is shown as well as individual gentamicin disappearance curves for 31 neonates who required dosing adjustment (Zone I = required increased dosage; Zone II = required decreased dosage). A single blood sample is drawn between 8 and 12 hours after the start of drug infusion. Any value falling within the Normal Zone is bordered by the following: upper 8 and 12 hour serum values = 3.5 and 2 mcg/ml; lower 8 and 12 hour serum values = 1.8 and 1 mcg/ml. Dosage adjustment
If the %RDR calculated is <25%, then reduce the dose by the calculated percent and continue dosing every 12 hours. If the %RDR calculated is > 25%, then increase the dosing interval to every 24 hours while keeping the dose at 2.5 mg/kg per dose. Recheck drug levels 1 to 2 hours prior to dosing. Acceptable levels would be between 1 and 2 mcg/ml. ReferenceLeff RD, Andersen RD, Roberts RJ. Simplified gentamicin dosing in neonates: a time- and cost-efficient approach. Pediatr Infect Dis 1984;3:208-212. Diuretic AgentsJeffrey L. Segar, MD
Footnotes
Effects of Drugs on the Fetus or NewbornDownload Effects of Drugs on the Fetus or Newborn Identifying Neonatal Abstinence Syndrome (NAS) and Treatment Guidelines University of Iowa Stead Family Children’s Hospital -11/2014 What is Neonatal Abstinence Syndrome? Screening
Jeffrey L. Segar, MD It has been reported that women account for approximately 30% of the drug-addicted population and the majority of them are of childbearing age. Thus, drug abuse not only affects the mother but may harm the fetus and child. Clinical manifestationsA. Signs of heroin withdrawal occur in 50-75% of infants born to addicted mothers and usually begin within the first 24-72 h of life.The incidence of withdrawal depends on several factors, including dosage, duration of addiction, and time of last maternal dose. Heroin use may be associated with delayed symptomatology up to 7 days, signs from methadone may occur even later. B. The signs of drug withdrawal may be subtle or overt, consisting of a combination of any of the following:
TreatmentA. Obtain a Social Service consultB. Swaddling - most infants can be managed in this mannerC. Small, frequent feedings if gastrointestinal signs presentD. MedicationsNeonatal Abstinence Scoring Systems exist to assess the severity of withdrawal. However, clinical expertise, rather than a numerical score, should be used in the decision to use medications. Generally, severe irritability interfering with feeding and sleep, vomiting and diarrhea, temperature instability, severe tachypnea, and seizures are indications for treatment. Schedule for Treatment of Infant in Withdrawal
Duration of treatment in neonatal heroin withdrawal may vary from 4 days to 6 weeks, longer with methadone withdrawal. Other drugsMarijuana
Cocaine
Alcohol
Download Neonatal Abstinence Syndrome and Treatment Guidelines What is Neonatal Abstinence Syndrome?
Jeffrey L. Segar, MD One of the most frequently asked questions of pediatricians, obstetricians and nurses concerns the effect of various drugs taken by the nursing mother on her infant. A comprehensive reference to guide you in your decision as to whether or not a mother receiving a given drug should continue to breast feed will be found in the literature. References include: Roberts, Drug Therapy in Infants (Chapter 11); Briggs, et al, Drugs in Pregnancy and Lactation, 1991; White and White, Breast feeding and Drugs in Human Milk, Vet Human Tox Suppl. I, Vol 22, 1980. There are only a few known categories of drugs which when given to the mother warrant the interruption of breast feeding. It may be possible to minimize infant drug exposure by instructing the mother to take the medication immediately after completing breast feeding or by collecting breast milk for subsequent feeding just prior to taking medication. If drug therapy in the mother is to be of short duration, interruption rather than complete termination of breast-feeding should be advised. The link below leads to a comprehensive database about maternal drugs in breast milk. https://www.ncbi.nlm.nih.gov/books/NBK501922/?report=classic Use of Drug Monitoring Levels in the NICUJonathan M. Klein, MD, Thomas N. George, MD, and Sarah B. Tierney,
PharmD General guidelines
Gentamicin
Vancomycin
Theophylline
Phenobarbital
Phenytoin/fosphenytoin
References:Lexi-Comp, Inc. Pediatric Drug Information. Accessed online. Updated annually. Jeffrey L. Segar, MD Purpose: To Determine Patient Drug Kinetic Parameters Enabling Optimal Dosage Selection When to use:Drug half-life studies are most valuable in cases of: A. drug with narrow therapeutic index (little difference between therapeutic and toxic blood levels). How to accomplish accurate T1/2 determination:In most situations, half-life studies should be done rather than single "peak" or "trough" studies - particularly in situations I.A - I.C above. A. Blood sampling times should be selected to assure maximum accuracy. This means that one should avoid sampling "too close to the time of administration" (drug still being infused) yet not sample at a time when the concentration of drug may be too low to chemically detect. All information regarding patient's weight, drug dose, dosing interval, time of administration, route of administration, and time blood samples were drawn should be provided. This information will then appear in the chart record and will allow accurate pharmacokinetic calculations to be made. A. Determination of T1/2: (First Order)
B. Optimal Dosing Schedule (T):
When to do T1/2 studies vs. single time blood level studiesSingle blood level determinations have only limited utility since they can be used for dosage adjustment only on a very limited scale. They are useful as a screening procedure to assure that adequate dosing is being accomplished. Drugs with relatively longer half-lives (very little difference in peak and trough levels) can ordinarily be followed by single blood levels determinations. When a single blood level is used for monitoring the progress of the patient, be sure to select a time which avoids problems of IV delivery time. Generally, a -2-3 hour single time point- following IV administration is best. TABLE 1: RECOMMENDED SINGLE BLOOD LEVEL SAMPLING TIMES
In general, T 1/2 studies are not absolutely needed until several doses of the drug have been given (1 to 2 days). The exception is the patient with severe organ dysfunction who will require repeated blood level determinations to adjust dosage. In these compromised patients, T 1/2 studies should be done after the first dose and before subsequent dosing. T 1/2 studies only need to be repeated if a marked change occurs in the patient's organ function status. TABLE 2: RECOMMENDED T 1/2 SAMPLING TIMES
*Sampling within 1 hr. of drug administration is likely to be confusing because some drug may still be in the process of being infused or absorbed. TABLE 3: USUAL THERAPEUTIC RANGE
Other ResourcesJeffrey L. Segar, MD The cause of apnea should be thoroughly investigated (see Pulmonary section). Only if no treatable cause can be found, the diagnosis of apnea of prematurity can be considered (diagnosis of exclusion). If necessary, central apnea of prematurity may be treated using one of the following drugs.
1 Further studies needed on bioavailability, toxicity, and long term efficacy. Potential toxicity with vehicle which contains benzyl alcohol. The drug of choice caffeine. If apnea persists despite appropriate doses, doxapram may replace caffeine. If response is still inadequate, both drugs may be combined. Jeffrey
L. Segar, MD and Sarah B. Tierney, PharmD Emergency Drug Doses
Jeffrey L. Segar, MD Definition (not fully clear):
Management should be directed towards correcting the underlying etiology. It is uncertain whether moderate hypertension associated with bronchopulmonary dysplasia requires therapy, since it is mostly transient. Renovascular hypertension can be managed pharmacologically. Pharmacologic Therapy for Neonatal Systemic Hypertension
Which action would the nurse take for a patient in status epilepticus?Place oral airway when possible. Stay with patient. Have another person notify physician. Suction as necessary to maintain adequate airway to avoid obstruction or possible aspiration.
What is a guideline for the nurse when administering phenytoin Dilantin intravenously?The drug should be injected slowly intravenously at a rate not exceeding 1-3 mg/kg/min or 50 mg per minute, whichever is slower. Continuous monitoring of the electrocardiogram and blood pressure is essential. The patient should be observed for signs of respiratory depression.
What is the therapeutic index of phenytoin?Phenytoin has a narrow therapeutic window, between 10-20 mg/L. Serum concentrations of phenytoin are monitored by measuring the total phenytoin concentration.
Which feature of phenytoin makes it most susceptible to drug interactions?Phenytoin is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism. Inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity.
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